TY - JOUR
T1 - Ultrasensitive DNA hypermethylation detection using plasma for early detection of NSCLC
T2 - A study in Chinese patients with very small nodules
AU - Chen, Chen
AU - Huang, Xiaojie
AU - Yin, Wei
AU - Peng, Muyun
AU - Wu, Fang
AU - Wu, Xia
AU - Tang, Jingqun
AU - Chen, Mingjiu
AU - Wang, Xiang
AU - Hulbert, Alicia
AU - Brock, Malcolm V.
AU - Liu, Wenliang
AU - Herman, James G.
AU - Yu, Fenglei
N1 - Publisher Copyright:
© 2020 The Author(s).
PY - 2020/3/5
Y1 - 2020/3/5
N2 - Purpose: We had previously developed highly sensitive DNA methylation detection to diagnose lung cancer in patients with pulmonary nodules. To validate this approach and determine clinical utility in Chinese patients with indeterminate pulmonary nodules, we assessed the diagnostic accuracy for early stage lung cancer in plasma samples. Experimental design: Patients with CT-detected small lung nodules (diameter ≤ 3.0 cm) were included. Cases (n = 163) had staged IA or IB non-small cell lung cancer (NSCLC), while controls (n = 83) had non-cancerous lesions. Promoter methylation of eight lung cancer-specific genes (CDO1, TAC1, SOX17, HOXA7, HOXA9, GATA4, GATA5, and PAX5) was detected using nanoparticle-based DNA extraction (MOB) followed by qMSP. Results: Methylation detection for CDO1, TAC1, SOX17, and HOXA7 in plasma was significantly higher in cases compared with the benign group (p < 0.001). The sensitivity and specificity for lung cancer diagnosis using individual gene was 41-69% and 49-82%. A three-gene combination of the best individual genes has sensitivity and specificity of 90% and 71%, with area under the receiver operating curve (AUC) of 0.88, (95% CI 0.84-0.93). Furthermore, three-gene combinations detected even the smallest lung nodules, with the combination of CDO1, SOX17, and HOXA7 having the overall best performance, while the combination of CDO1, TAC1, and SOX17 was best in tumor sizes less than 1.0 cm. Conclusions: Using modified MOB-qMSP, high sensitivity and specificity, for the detection of circulating tumor DNA was obtained for early stage NSCLC. This strategy has great potential to identify patients at high risk and improve the diagnosis of lung cancer at an earlier stage. Graphical Abstract: [Figure not available: see fulltext.]
AB - Purpose: We had previously developed highly sensitive DNA methylation detection to diagnose lung cancer in patients with pulmonary nodules. To validate this approach and determine clinical utility in Chinese patients with indeterminate pulmonary nodules, we assessed the diagnostic accuracy for early stage lung cancer in plasma samples. Experimental design: Patients with CT-detected small lung nodules (diameter ≤ 3.0 cm) were included. Cases (n = 163) had staged IA or IB non-small cell lung cancer (NSCLC), while controls (n = 83) had non-cancerous lesions. Promoter methylation of eight lung cancer-specific genes (CDO1, TAC1, SOX17, HOXA7, HOXA9, GATA4, GATA5, and PAX5) was detected using nanoparticle-based DNA extraction (MOB) followed by qMSP. Results: Methylation detection for CDO1, TAC1, SOX17, and HOXA7 in plasma was significantly higher in cases compared with the benign group (p < 0.001). The sensitivity and specificity for lung cancer diagnosis using individual gene was 41-69% and 49-82%. A three-gene combination of the best individual genes has sensitivity and specificity of 90% and 71%, with area under the receiver operating curve (AUC) of 0.88, (95% CI 0.84-0.93). Furthermore, three-gene combinations detected even the smallest lung nodules, with the combination of CDO1, SOX17, and HOXA7 having the overall best performance, while the combination of CDO1, TAC1, and SOX17 was best in tumor sizes less than 1.0 cm. Conclusions: Using modified MOB-qMSP, high sensitivity and specificity, for the detection of circulating tumor DNA was obtained for early stage NSCLC. This strategy has great potential to identify patients at high risk and improve the diagnosis of lung cancer at an earlier stage. Graphical Abstract: [Figure not available: see fulltext.]
KW - Biomarker
KW - DNA methylation
KW - Early detection
KW - Lung cancer
KW - Plasma
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U2 - 10.1186/s13148-020-00828-2
DO - 10.1186/s13148-020-00828-2
M3 - Article
C2 - 32138766
AN - SCOPUS:85081267108
SN - 1868-7075
VL - 12
JO - Clinical Epigenetics
JF - Clinical Epigenetics
IS - 1
M1 - 828
ER -